10.6084/m9.figshare.11663610.v1
Ronghua Liu
Ronghua
Liu
Yucan Zhang
Yucan
Zhang
Peiwen Sun
Peiwen
Sun
Changxiu Wang
Changxiu
Wang
Figure 5C from DDP-resistant ovarian cancer cells-derived exosomal microRNA-30a-5p reduces the resistance of ovarian cancer cells to DDP
The Royal Society
2020
ovarian cancer
exosomes
MicroRNA-30a-5p
SRY-box 9
DDP
sensitivity
drug resistance
2020-01-20 17:20:27
Figure
https://rs.figshare.com/articles/figure/Figure_5C_from_DDP-resistant_ovarian_cancer_cells-derived_exosomal_microRNA-30a-5p_reduces_the_resistance_of_ovarian_cancer_cells_to_DDP/11663610
Exosomes carrying microRNAs (miRNAs) have been demonstrated to play critical roles in the regulation of development, growth and metastasis of cancer. Bioinformatic predictions identified differentially expressed SRY-box 9 (SOX9) in OC, and the regulatory miRNA miR-139-5p. Here, we aim to evaluate the function of exosomal miR-139-5p in the sensitivity of ovarian cancer (OC) cells to cis-diamminedichloroplatinum(II) (DDP). Expression pattern of miR-139-5p and SOX9 in ovarian cancer cells (SKOV3) and DDP-resistant cells (SKOV3/DDP) was identified using reverse transcription quantitative polymerase chain reaction and western blot analysis. The relationship between miR-139-5p and SOX9 was validated using dual-luciferase reporter assay. SKOV3/DDP cell line was developed and introduced with miR-30a-5p mimic to analyse the effects of miR-30a-5p on resistance to DDP. The <i>in vitro</i> and <i>in vivo</i> effects of exosomal miR-30a-5p on resistance of SKOV3 cells to DDP were assessed in a co-culture system of exosomes and OC cells as well as in tumour-bearing nude mice. High expression of SOX9 and low expression of miR-30-5p were witnessed in OC. Furthermore, miR-30-5p, a downregulated miRNA in SKOV3/DDP cells, increased the rate of cell apoptosis and enhanced the sensitivity of SKOV3/DDP cells to DDP by targeting SOX9. Moreover, exosomes carrying miR-30a-5p were identified to sensitize SKOV3/DDP cells to DDP both <i>in vitro</i> and <i>in vivo</i>. These data together supported an important conclusion that DDP-resistant OC cell-derived exosomal miR-30a-5p enhanced cellular sensitivity to DDP, highlighting a potential strategy to overcome drug resistance.